Our previous studies have determined that sequential development of Leishmania promastigotes from a noninfective to an infective stage accompanies the growth of parasites both within culture and the sandfly vector. Infective or metacyclic L. major promastigotes can now be purified from culture on the basis of their loss of binding sites for the lectin peanut agglutinin (PNA). A metacyclic stage specific surface antigen (116,000 M.W.) has been detected on the basis of Western blot analysis and immunoprecipitation of surface labeled organisms. In addition, a monoclonal antibody has been produced which binds strongly to the surface of metacyclic promastigotes and only weakly to log phase parasites. The role of these surface changes in the development of promastigotes within the sandfly as well as their ability to visit the leishmanicidal activities of normal macrophages and serum are currently being studied. The immunology of human visceral leishmaniasis is being studied in a collaborative project recently initiated by Dr. Frank Neva with the Rajendra Memorial Research Institute in Patna, India. In initial studies on 18 patients with acute visceral disease responsiveness to leishmanial antigens was found to be profoundly suppressed. Removal of OKT8+ lymphocytes did not reconstitute these responses. Kala-azar patients maintained good responses to mitogens and PPD. The immunological basis of this specific unresponsiveness will be pursued during future visits.